Immune responses induced by vaccination can be categorized broadly into humoral or cellular types. A humoral response is typically desired to protect against viral or bacterial invaders, whereas immunity against virally infected cells and cancer cells typically involves a cell mediated response. Humoral immunity is typified by high levels of antibody production by B cells, whereas cellular immunity is characterized by increased activation of cytotoxic CD8 T lymphocytes.
The type of immunity induced by a vaccine largely depends on the type of adjuvant included in the vaccine. Adjuvants based on palmitic acid, such as dipalmitoyl-S-glyceryl-cysteine (PAM2Cys) and tripalmitoyl-S-glyceryl-cysteine (PAM3Cys) and variants thereof, have been reported to enhance humoral and cellular responses against a variety of antigens. For practical reasons, the solubility of such adjuvants has been typically improved with the addition of hydrophilic non-immunogenic amino acid residues (Lysines for example). Such adjuvants have been mixed with antigen but in many instances palmitic acid based adjuvants have been covalently linked to antigens before administering to a subject. Palmitic acid adjuvants have also been co-delivered with antigen using liposomes as carriers. Protein based and carbohydrate based antigens have been combined with palmitic acid adjuvants to produce antibody and T cell responses. The use of palmitic acid adjuvants for cancer applications is well documented, with activity mediated primarily by cellular responses.
Although palmitic acid derivatives are known to proliferate B cells, induce isotypic switching, induce differentiation of human B lymphocytes to IgG secreting plasma cells and increase expression of several co-stimulatory molecules (MHC I, II, CD80, etc), reports of palmitic acid adjuvants inducing antibody responses has varied in the literature from being able to enhance antibody responses to not being particularly useful for generating such responses.
Thus, there remains a need for the development of vaccine compositions for generating strong humoral responses against a variety of antigens. The present invention provides vaccine compositions that contain a lipid-based adjuvant and are particularly useful for inducing a high level of antibodies in immunized subjects.